WHAT YOU NEED TO KNOW
- Researchers analyzed 51 intervention studies using more than 110 DNA methylation biomarkers associated with aging.
- Healthy diets and regular exercise were linked to reductions in epigenetic aging measurements.
- Metformin, semaglutide, and anti-TNF therapies produced the largest average effects, but researchers warned against using them solely to slow aging.
- Supplements showed limited and inconsistent evidence of effects on aging biomarkers.
- Biomarker changes do not prove that an intervention improves health, preserves function, or extends life.
Aging is inevitable, but biological age can offer a window into how well a person is aging. Unlike chronological age, it reflects physiological condition rather than simply the amount of time since birth.
Researchers can estimate biological age through blood biomarkers known as epigenetic clocks, which examine methyl groups attached to DNA. Previous research has found that these epigenetic tags change throughout a person’s lifetime.
A study published in Nature Medicine examined whether dietary, lifestyle, and pharmacological interventions could alter DNA methylation patterns associated with aging. The findings linked several interventions with changes suggesting a slower pace of biological aging.
Researchers combined data from 51 intervention studies focused on aging and measured more than 110 DNA methylation biomarkers. They evaluated the effects of diet, exercise, certain medications, and supplements available without a prescription.
The analysis used the same panel of 16 epigenetic clocks and 94 additional DNA methylation biomarkers across the collected data. This standardized method allowed the researchers to compare how different measures responded to various interventions.
Some newer biomarkers appeared more responsive than clocks primarily designed to predict chronological age. Şebnem Ünlüişler, Chief Longevity Officer and genetic engineer at the London Regenerative Institute, identified DunedinPACE and PCGrimAge as particularly notable measures.
Two lifestyle approaches were effective in reducing epigenetic aging according to the biomarker results. These were following a healthy diet, including Mediterranean diets and diets lower in carbohydrates or fat, and exercising regularly.
The largest effects appeared with certain medications. Metformin, a treatment for type 2 diabetes, semaglutide, a GLP-1 agonist prescribed for type 2 diabetes and weight control, and anti-TNF therapies all significantly decreased age across the 16 epigenetic clocks.
“Pharmacological interventions showed the largest average effects, while lifestyle and dietary interventions tended to produce more consistent responses across different biomarkers,” Ünlüişler told Medical News Today. The contrast suggests that the type and consistency of biomarker responses varied by intervention.

Those findings do not establish that the medications should be used by healthy people seeking to slow aging. Ünlüişler cautioned that the drug results were scientifically interesting but should not be treated as evidence supporting such use.
Some medication studies involved specific patient populations. According to Ünlüişler, the observed biomarker changes may partly reflect improvements in disease, inflammation, or metabolic health rather than a direct reversal of aging.
Supplements delivered far less encouraging results, with little evidence that they affected the aging biomarkers. “The evidence for supplements was limited and inconsistent,” corresponding author Raghav Sehgal, PhD, Associate Research Scientist in Psychiatry at the Yale University School of Medicine, said.
Sehgal noted that supplements may still be valuable for people with specific deficiencies or medical needs. For generally healthy people, however, many claims about slowing aging remain ahead of the available evidence.
The central limitation is that a changing biomarker does not prove an intervention slows aging. “Biomarkers are useful because they may let us see biological changes over months or years, rather than having to wait decades for outcomes like disease or death. But they are not a replacement for long-term studies,” Sehgal said.
Researchers must still determine whether biomarker changes translate into better health, improved function, or longer lives. Ünlüişler similarly said epigenetic clocks should currently be regarded as promising research tools rather than definitive measures of individual health.
“There is not yet a single intervention proven to broadly slow aging in humans,” Sehgal said. “The best-supported measures remain fairly unglamorous: not smoking, exercising regularly, eating well, sleeping adequately, and managing blood pressure, cholesterol, and diabetes.”
Ünlüişler agreed that aerobic and resistance exercise, a balanced Mediterranean style diet, healthy weight maintenance, limited alcohol, and sufficient consistent sleep support health over time. Proper management of high blood pressure, high cholesterol, and diabetes is also important.
“We cannot change our chronological age, but we can influence many of the biological processes that determine how well we age,” Ünlüişler said. For now, established healthy behaviors have stronger evidence for supporting healthspan than any single supplement or treatment marketed for aging.
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